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Inhibitory effects of the combination of HER-2 antisense oligonucleotide and chemotherapeutic agents used for the treatment of human breast cancer.
- Source :
-
Cancer gene therapy [Cancer Gene Ther] 2001 Oct; Vol. 8 (10), pp. 728-39. - Publication Year :
- 2001
-
Abstract
- Poor response to chemotherapy in patients with breast cancer is often associated with overexpression of HER-2/neu. Interference with HER-2 mRNA translation by means of antisense oligonucleotides might improve the efficacy of chemotherapy. To test this hypothesis, eight breast cancer cell lines and a normal human fibroblast cell line were examined for their level of HER-2 expression, their sensitivity to phosphorothioate antisense oligonucleotides (AS HER-2 ODN), and to various chemotherapeutic agents, and the combination of the two. No correlation was found between the intrinsic HER-2 level and either the sensitivity to a particular chemotherapeutic agent alone, or the amount of growth inhibition observed with a specific AS HER-2 ODN concentration. Although sequence specificity and extent of AS HER-2 ODN inhibition of HER-2 synthesis were somewhat higher in the HER-2 overexpressing MDA-MB-453 and SK-BR-3 cells, we found that antisense treatment significantly sensitized all of the breast cancer cells, even MDA-MB-231 and MDA-MB-435 cells, with approximately basal levels of HER-2, to various chemotherapeutic agents. In addition, the combination of AS HER-2 ODN and taxol was shown to synergistically induce apoptosis in MDA-MB-435. These results demonstrate that overexpression of HER-2 would not be a prerequisite for the effective use of AS HER-2 ODN as a combination treatment modality for breast cancer and suggest that the use of AS HER-2 ODN, as part of a combination treatment modality, need not be limited to breast tumors that display elevated levels of HER-2.
- Subjects :
- Apoptosis
Blotting, Western
Breast Neoplasms metabolism
Cell Division drug effects
Drug Therapy, Combination
Female
Fibroblasts drug effects
Fibroblasts metabolism
Flow Cytometry
Humans
Poly(ADP-ribose) Polymerases metabolism
Proto-Oncogene Proteins c-bcl-2 metabolism
Receptor, ErbB-2 metabolism
Tumor Cells, Cultured metabolism
Antineoplastic Agents pharmacology
Breast Neoplasms drug therapy
Oligonucleotides, Antisense pharmacology
Receptor, ErbB-2 genetics
Tumor Cells, Cultured drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0929-1903
- Volume :
- 8
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cancer gene therapy
- Publication Type :
- Academic Journal
- Accession number :
- 11687896
- Full Text :
- https://doi.org/10.1038/sj.cgt.7700359